What is the management approach for a patient with hepatocellular carcinoma (HCC), portal vein tumor thrombus, and cirrhosis, who is also on antiretroviral therapy (ART) for Human Immunodeficiency Virus (HIV)?

Management of HCC with Portal Vein Tumor Thrombus and Cirrhosis in HIV-Positive Patients on ART

For a patient with HCC, portal vein tumor thrombus (PVTT), and cirrhosis who is on antiretroviral therapy, first-line systemic therapy with atezolizumab plus bevacizumab is the recommended treatment, provided the patient has Child-Pugh A liver function and adequate performance status (ECOG 0-1). 1

Initial Assessment and Staging

The presence of PVTT automatically classifies this patient as Barcelona Clinic Liver Cancer (BCLC) Stage C (advanced stage), regardless of other tumor characteristics. 1 This staging determination is critical because it directs treatment away from curative approaches and toward systemic therapy or carefully selected locoregional options. 2, 3

Key parameters to assess immediately:

• Liver function: Child-Pugh classification must be determined—only Child-Pugh A patients are candidates for systemic therapy. 1 Child-Pugh B may be considered in highly selected cases, while Child-Pugh C patients should receive best supportive care only. 4

• Performance status: ECOG performance status 0-1 is required for systemic therapy eligibility. 5 ECOG 2 may be considered with caution, but ECOG 3-4 contraindicates active treatment. 1

• Extent of PVTT: Classification into Vp1-4 is essential, as main portal trunk involvement (Vp4) has the worst prognosis and most limited treatment options. 2, 6

• HIV status: Ensure viral suppression on ART and adequate CD4 count, as immunosuppression may affect treatment tolerance and outcomes. 4

First-Line Systemic Therapy

Atezolizumab plus bevacizumab is now the standard first-line systemic therapy for advanced HCC, having demonstrated superior overall survival compared to sorafenib. 1, 4 This combination targets both immune checkpoint inhibition and angiogenesis pathways. 2

Critical contraindications to bevacizumab:

• Active or recent gastrointestinal bleeding (common in cirrhotic patients with portal hypertension). 1
• Untreated esophageal varices requiring screening endoscopy before initiation. 1
• Uncontrolled hypertension. 5

If bevacizumab is contraindicated, lenvatinib is the alternative first-line option, though it was not studied in patients with main portal trunk invasion (Vp4). 3

HIV-Specific Considerations

Continue antiretroviral therapy without interruption throughout HCC treatment. 4 There are no absolute contraindications to combining systemic HCC therapy with modern ART regimens, though drug-drug interactions should be reviewed. 4

Monitor for:

• Hepatotoxicity from both ART and systemic therapy, requiring liver function tests every 2 weeks initially, then monthly. 4
• Immune reconstitution effects if CD4 count is suboptimal. 4
• HBV or HCV coinfection status, as these require concurrent antiviral therapy to prevent reactivation during immunosuppression or chemotherapy. 4

Locoregional Therapy Considerations

While systemic therapy is the guideline-recommended approach for PVTT, emerging evidence suggests that combining transarterial chemoembolization (TACE) with systemic therapy may improve outcomes in selected patients with Vp1-3 PVTT (not involving main portal trunk). 2, 6, 7

TACE should be considered if:

• PVTT is limited to segmental or sectoral branches (Vp1-2). 6, 7
• Liver function remains Child-Pugh A. 1
• No contraindications exist (decompensated cirrhosis, complete portal vein occlusion, or hepatofugal flow). 1

Transarterial radioembolization (TARE) with Y90 microspheres is an alternative locoregional approach that may be better tolerated than TACE in patients with PVTT due to its minimally embolic effect. 1 However, it should not replace systemic therapy as the primary treatment. 1

Second-Line Systemic Therapy Options

If disease progresses on atezolizumab plus bevacizumab or if first-line therapy is not tolerated:

• Regorafenib is approved for patients who tolerated prior sorafenib (≥400 mg daily for ≥20 of the last 28 days before progression). 5 It demonstrated median overall survival of 10.6 months versus 7.8 months with placebo in the RESORCE trial. 5

• Cabozantinib is another second-line option after sorafenib failure. 3

• Ramucirumab can be used in patients with AFP ≥400 ng/mL after sorafenib. 3

Treatments to Avoid

The following are NOT recommended:

• Surgical resection is contraindicated in the presence of PVTT with underlying cirrhosis due to prohibitive perioperative mortality risk and extremely high recurrence rates. 1, 8

• Liver transplantation is an absolute contraindication when macrovascular invasion (PVTT) is present. 1

• Thermal ablation (RFA/microwave) is ineffective for PVTT due to heat-sink effect from blood flow. 3

• Sorafenib monotherapy provides only marginal benefit (median survival 2.8 months in PVTT patients) and has been superseded by atezolizumab plus bevacizumab. 2, 3

Monitoring and Supportive Care

Surveillance imaging with contrast-enhanced CT or MRI should be performed every 6-8 weeks to assess treatment response using mRECIST criteria for HCC. 5

Manage cirrhosis complications aggressively:

• Screen for and treat esophageal varices. 1
• Monitor for hepatic encephalopathy, particularly if using opioids for pain (always co-prescribe osmotic laxatives). 4
• Avoid NSAIDs completely due to bleeding risk and renal toxicity. 4
• Use acetaminophen ≤3 g/day for pain management. 4

Nutritional support is critical, as cachexia and malnutrition worsen prognosis in HCC patients. 4

Prognosis

Untreated HCC with PVTT has a median survival of only 2-4 months. 3, 6 With modern systemic therapy, median overall survival can be extended to 10-17 months depending on the extent of PVTT and liver function. 5, 2 Main portal trunk involvement (Vp4) carries the worst prognosis even with treatment. 6

Critical Pitfalls to Avoid

• Never delay systemic therapy while pursuing locoregional options in patients with PVTT—systemic therapy should be the backbone of treatment. 2, 9

• Never interrupt ART during HCC treatment, as this risks HIV progression and opportunistic infections. 4

• Never use bevacizumab without screening for varices, as bleeding risk is significantly elevated in cirrhotic patients. 1

• Never consider curative surgical approaches (resection or transplant) in the presence of PVTT, as these are absolute contraindications. 1